WO2004017811A2 - High-resolution magnetoencephalography system and method - Google Patents

Abstract

According to certain embodiments of the present invention, there is provided a magnetoencephalography and method employing a portable cart having a SQUID dewar mounted in an inverted manner thereon, and having a headrest assembly mounted on the cart for supporting the head of a patient and forming a portion of the dewar. The headrest assembly includes an array of magnetic sensors of the SQUID dewar for responding to electrical activity of the brain of the head.

Description

HIGH-RESOLUTION MAGNETOENCEPHALOGRAPHY SYSTEM AND METHOD

Related Applications The present application is related to U.S. non-provisional patent application entitled "HIGH-

RESOLUTION MAGNETOENCEPHALOGRAPHY SYSTEM, COMPONENTS, AND

METHOD," filed June 26, 2003, Serial No. unknown/unassigned, which is incorporated

herein by reference, and to U.S. non-provisional patent application entitled "HIGH-

RESOLUTION MAGNETOENCEPHALOGRAPY SYSTEM AND METHOD," filed June 26,

2003, Serial No. unknown/unassigned, which is incorporated herein by reference.

The subject patent application also claims priority to U.S. provisional patent

application, entitled HIGH-RESOLUTION MAGNETOENCEPHALOGRAPHY SYSTEM,

Serial No. 60/393,045, filed June 28, 2002, which is incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The invention relates to medical diagnostic systems and methods. In particular,

the invention relates to a system and method for obtaining high-resolution

encephalographs.

Related Art The information contained in this section relates to the background of the art of

the present invention without any admission as to whether or not it legally constitutes prior art.

The following is a list of articles relating to various diagnostic techniques

contemplated for assessing brain functions, as follows: Ahonen, A. I., Hamalainen, M. S., Kajola, M. J., Knuutila, J. E. T., Laine, P.

P., Lounasmaa, 0. V., Parkkonen, L. T., Simola, J. T., and Tesche, C. D. 122 channel SQUID instrument for investigating the magnetic signals from the human brain. Physica

Scripta, 1993, T49: 198-205; Barth, D. S., Sutherling, W., Broffman, J., and Beatty, J. Magnetic localization of a dipolar current source implanted in a sphere and a human cranium. Electroenceph. in. Neurophvsio 1986, 63: 260-273;

Buchanan, D. S., Crum, D. B., Cox, D., & Wikswo, J. P. jr. MicroSQUID: A

close-spaced four channel magnetometer. In S. J. Williamson et al., (eds.), Advances in

Biomagnetism, Plenum Press, New York, 1989, pp. 677-679; Curio, G., Mackert, B.-M., Abraham-Fuchs, K., and Harer, W. (1994) High-

frequency activity (600 Hz) evoked in the human primary somatosensory cortex: a survery

of electric and magnetic recordings. In C. Patev et al., eds. Oscillatory Event-Related Brain

Dynamics. Penum Press, New York, pp. 205-218;

Curio, G., Mackert, B.-M., Burghoffm M., Koetitz, R., Abraham-Fuchs, K., and Harer, W. (1994) Localization of evoked neuromagnetic 600 Hz activity in the cerebral

somatosensory system. Electroenceph. din. Neurophvsiol., 91 :483-487;

De Weerd, A. W. Atlas of EEG in the first months of life. El Sevier, New York,

1995;

Dreyfus-Brisac, C. The electroencephalogram of the premature infant and full- term newborn: normal and abnormal development of waking and sleeping patterns. In P. Kellaway and I. Petersen (eds.), Neurological and electroencephaloαraphic correlative

studies in infancy. Grune and Stratton, New York, 1964, pp. 186-207;

Dreyfus-Brisac, C. The electroencephalogram of the premature infant. World

Neuro , 1962, 3: 5-15; Dreyfus-Brisac, C, Samson, D., Blanc, C, and Monod, N.. L'electroencephalogramme de I'enfant normal de moins de 3 ans. Etud. neo-natal. 1958, 7: 143-175;

Emerson, R. G., Sgro, J. A., Pedley, T. A., Hauser, W. A. (1988) State- dependent changes in the N20 component of the median nerve somatosensory evoked potential. Neurology. 38: 64-68.

Erasmie, U., & Ringertz, H. Normal width of cranial sutures in the neonate and

infant. Acta Radiol. Diagnosis, 1976, 17: 565-572;

Geselowitz, D. B. On the magnetic field generated outside an inhomogeneous

volume conductor by internal current sources. IEEE Trans. Mag., 1970, 6: 346-347;

Gevins, A., Le, J., Leong, H., McEvoy, L. K., and Smith, M. E. (1999)

Demurring. J. Clin. Neurophvsiol. 16: 204-213;

Gevins, A., Le, J., Martin, N. K., Brickett, P., Desmond, J., and Reutter, B.

High resolution EEG: 124-channel recording, spatial deblurring and MRI integration methods. Electroenceph. clin. Neurophvsiol., 1994, 90: 337-358;

Gobbele, R., Buchner, H., and Curio, G. (1998) High-frequency (600 Hz) SEP

activities originating in the subcortical and cortical human somatosensory system. Electroenceph. din. Neurophvsiol., 108: 182-189;

Goff, W. R., Allison, T., and Vaughan, H. G., Jr. (1978) The functional

neuroanatomy of event related potentials. In: Event-related brain potentials in man. E.

Callaway, P. Tueting, and S. H. Koslow (Eds.), Academic Press, New York San Francisco

London, pp. 1-79;

Grynszpan, F. and Geselowitz, D. B. (1973) Model studies for the

magnetocardiogram. Biophvs. J., 13: 911-925; Hamalainen, M. S., and llmoniemi, R. (1994) Interpreting magnetic fields of

the brain: minimum norm estimates. Med. Biol. Eng. Comp.. 32:35-42;

Hamalainen, M. S., and Santas, J. (1989) Realistic conductivity geometry

model of the human head for interpretation of neuromagnetic data. IEEE Trans. Biomed.

Eng., 36:165-171 ;

Hamalainen, M., and Sarvas, J. Realistic conductivity geometry model of the

human head for interpretation of neuromagnetic data. IEEE Trans. Biomed. Eng.. 1989, 36:

165-171 ;

Hansman, C. F. (1966) Growth of interorbital distance and skull thickness as

observed in roentgenographic measurements. Radiology, 86:87-96;

Hansman, C. F. Growth of interorbital distance and skull thickness as

observed in roentgenographic measurements. Radiology, 1966, 86: 87-96;

Hashimoto, I., Mashiko, T., and Imada, T. (1996a) Somatic evoked high-

frequency magnetic oscillations reflect activity of inhibitory interneurons in the human

somatosensory cortex. Electroenceph. clin. Neurophvsiol., 100:189-203;

Hashimoto, I., Papuashvili, N., Xu, C. and Okada, Y. C. (1996b) Neuronal

activities from a deep subcortical structure can be detected magnetically outside the brain

in the porcine preparation. Neurosci. Lett. 206:25-28;

Haueisen, J., Heuer, T., Nowak, H., Liepert, J., Weiller, C, Okada, Y. C, and

Curio, G. (2000a) The influence of lorazepam on somatosensory evoked fast frequency

(600 Hz) activity in MEG. Brain Res, in press;

Haueisen, J., Schack, B., Meier, T., Nowak, H., Weiller, C, Curio, G., and

Okada, Y. C. (2000b) Time-frequency analysis of somatosensory evoked short latency

cortical activity in MEG. To be submitted to Clinical Neurophysiology; Humphrey, D. R. (1968a) Re-analysis of the antidromic cortical response. I.

potentials evoked by stimulation of the isolated pyramidal tract. Electroenceph. clin. Neurophvsiol., 24:116-129;

Humphrey, D. R. (1968b) Re-analysis of the antidromic cortical response. Ii.

on the contribution of cell discharge and PSPs to the evoked potentials. Electroenceph. din. Neurophvsiol., 25:421-442;

Kaufman, L., Okada, Y., Brenner, D., and Williamson, S. J. (1981) On the

relation between somatic evoked potentials and fields. Int. J. Neurosci., 15: 223-239;

Le, J., Menon, V., and Gevins, A. Local estimate of surface Laplacian derivation on a realistically shaped scalp surface and its performance on noisy data.

Electroenceph. din. Neurophvsiol., 1994, 92: 433-441;

Lusted, L. B., and Keats, T. E. Atlas of roentgenographic measurement. Year

Book Publishers, Chicago, 1978;

Mackert, B.-M., Weisenbach, S., Nolte, G., and Curio, G. (2000) Rapid recovery (20 ms) of human 600 Hz electroencephalographic wavelets after double

stimulations of sensory nerves. Neurosci. Lett., 286:83-86;

Okada YC, Lahteenmaki A, Xu C (1999a) Comparison of MEG and EEG on

the basis of somatic evoked responses elicited by stimulation of the snout in the juvenile

swine. Clin Neurophysiol 110:214-229; Okada YC, Lahteenmaki A, Xu C (1999b) Experimental analysis of distortion

of magnetoencephalography signals by the skull. Clin Neurophysiol 110:230-238;

Okada YC, Shah B, Huang J-C (1994) Ferromagnetic high-permeability alloy

alone can provide sufficient low-frequency and eddy-current shieldings for biomagnetic

measurements. IEEE Trans Biomed Eng 41:688-697; Okada, Y. C, Shah, B. and Huang, J.-C. (1994) Ferromagnetic high-

permeability alloy alone can provide sufficient low-frequency and eddy-current shieldings

for biomagnetic measurements. IEEE Trans. BME, 41 : 688-697;

Roark, R. J. and Young, W. C. Formulas for stress and strain. McGraw-Hill,

New York, 1975;

Sunshine, P. Epidemiology of perinatal asphyxia. In: D. K. Stevenson and P.

Sunshine, (eds.), Fetal and neonatal brain injury: Mechanisms, management and the risks

of practice. Oxford Univ. Press, New York, 1997, pp. 3-23;

Sunshine, R. (1997) Epidemiology of perinatal asphyxia. In: D. K. Stevenson

and P. Sunshine, (eds.), Fetal and neonatal brain iniurv: Mechanisms, management and the

risks of practice. Oxford Univ. Press, New York, pp. 3-23;

Tharp, B. Use of the electroencephalogram in assessing acute brain damage

in the newborn. In: D. K. Stevenson and P. Sunshine, (eds.), Fetal and

neonatal brain injury: Mechanisms, management and the risks of practice. Oxford Univ.

Press, New York, 1997, pp. 287-301 ;

Volpe, J. J. Neurology of the new born. W. B. Sanders, Philadelphia, PA,

2000; and

Yamada, T., Kameyama, S., Fuchigami, Y., Nakazumi, Y., Dickens, Q. S.,

and Kimura, J. (1988) Changes of short latency somatosensory evoked potential in sleep.

Electroenceph. clin. Neurophvsiol., 70: 126-136. The foregoing articles are each

incorporated herein by reference.

The need for finding useful diagnostic techniques is becoming increasingly urgent

today in assessing brain functions of infants. With advances in medicine, more and

more pre- and full-term newboms survive even with neurological disabilities (Sunshine, 1997; Volpe, 2000). According to Sunshine (1997), the number of newborns with

neurological impairments is quite large. The incidence of perinatal asphyxia is between

about 2/1000 and about 47/1000. Between about 4% and about 26% of those newborns

who survive such an event will have severe neurological deficits. The incidence of

hypoxemic-ischemic encephalopathy in term or near-term infants is between about 3/1000 and 8/1000. Handicapped survivors may be as high as about 42% in such

cases. The incidence of infants with neonatal seizures is between about 2/1000 and

about 9/1000. The incidence of handicaps in the survivors is between about 11% and about 50%. The incidence of moderate-to-severe cerebral palsy in infants who survive

the neonatal period is between about 1/1000 and 3/1000. The prevalence of severe

mental retardation is between about 3/1000 and about 4/1000 school-age children. The

incidence of mild mental retardation is between about 23/1000 and about 30/1000 in the

same population. According to Volpe (2000), the percentage of preterm infants with proven periventricular white matter injury is about 45% for those with birth weight of less

than about 1500g, about 38% for those with gestational age of less than about 33 weeks

and about 24% for those with gestational age of less than about 38 weeks. The

percentage of asphyxiated term infants with some form of central nervous system injury is as high as about 62%, a common form of the injury being the parasagittal cerebral injury. Infants with germinal matrix hemorrhage is between about 23% and about 32%

of all births delivered through the vaginal route when the delivery lasts more than six

hours.

Survival of neurologically impaired neonates raises an important responsibility for the health care community in this country. Currently, electroencephalography (EEG) is used to monitor electrical activity of the brain of newborns (Sunshine, 1997). The use of EEG for perinatal monitoring was started in the late 1950's (Dreyfus-Brisac et al., 1958; Dreyfus-Brisac, 1962, 1964). Its use is increasing in recent years due to its usefulness

in staging the development of the nervous system, in detecting the presence of hypoxic and intracranial injuries, in providing the prognosis of recovery and in differential

diagnosis of seizures from non-seizures in paroxysmal motor behavior (Tharp, 1997; de

Weerd, 1995). The staging is useful in detecting a delay or an arrest in brain

development. The waveforms and spatial topography such as hemispheric asymmetry of spontaneous EEG are also useful for detecting the presence of a tumor or a necrotic

area in the brain. In order for magnatoencephalography (MEG) to become useful as a clinical

electrophysiological monitoring technique, complementing EEG, it may be desirable for

certain applications to have a MEG instrument which may be different from the conventional whole-head MEG instruments. In this regard, to be competitive with EEG instrumentation, a useful MEG instrument must be functional in any ordinary clinical

rooms without any special cumbersome electromagnetic shielding such, for example, as

a large and expensive, special purpose magnetically shielded room being currently used

when conventional MEG techniques are employed.

Prior known MEG systems (such as those manufactured by Canadian Thin Films

or CTF, Vancouver, Canada, 4-D Neuroimaging, San Diego, CA, and Helsinki, Finland)

are relatively large and heavy, and are used mostly in an expensive magnetically

shielded room.

In order to use an MEG system to detect infant brainwaves with a sufficient high

resolution, it would be desirable to be able to position the MEG sensors in very close proximity to the head of the infant patient. This would necessitate maintaining such close spacing between the MEG sensors and the patient's head without altering the

spacing to any substantial extent during the use of this system.

The spacing between the patient's head and the sensor should be precisely

maintained within reasonable tolerances for at least some applications. Due to the

different coefficients of thermal expansion of the various components, this gap or

spacing between the head and the sensors may be difficult to maintain in the presence

of temperature changes for certain applications. Such temperature changes occur, for

example, when the SQUID dewar warms from cryogenic temperatures toward room

temperature. Also, when the dewar is cooled to its cryogenic temperatures, the

components tend to change dimensionally for some applications.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 A is a diagrammatic illustration of a high-resolution magneto-

encephalography (MEG) system according to one embodiment of the present invention;

Fig. 1B is a diagrammatic cross-sectional side view of the system illustrated in

Fig. 1A;

Fig. 2A is a cross-sectional diagrammatic view of one embodiment of the headrest

assembly of the system of Fig. 1 A;

Fig. 2B is a diagram illustrating the wall thickness of a portion of the headrest of

the headrest assembly of Fig. 2A;

Fig. 3 is a diagrammatic view of the rear surface of the headrest of Fig. 2B and

the headrest and illustrates one embodiment of the arrangement of sensor modules of

the headrest assembly of Fig. 2;

Fig. 4 is a diagram illustrating a single 4-channel sensor module; Figs. 5A, 5B and 5C illustrate one embodiment of a 4-channel module according to the present invention;

Figs. 6A, 6B and 6C illustrate a coil form for a pickup coil of the module illustrated

in Figs. 5A, 5B and 5C;

Fig. 6D and 6E illustrates a coil form for the cancellation coil of the module

illustrated in Figs. 5A, 5B and 5C;

Figs. 7 and 8 are charts illustrating noise spectra for a 4-channel module with

simulated dewar noise;

Figs. 9A and 9B are charts showing representative samples of the somatic

evoked magnet fields (SEFs) produced by piezoelectric vibratory stimulations and SEFs

produced by air puff stimulations;

Fig. 10 is a chart showing SEFs that are produced by a vibratory stimulation as a

function of number of epochs in the average;

Fig. 11 illustrates charts showing SEFs measured on a plane above the skull of

the piglet;

Fig. 12 illustrates charts showing an outline of the somatic evoked potential

measurement area on the skull with a square hole over the left hemisphere;

Fig. 13A illustrates charts showing the distortions due to conductivity differences;

Fig. 13B illustrates charts illustrating the Laplacian estimates of currents emerging

through a filter paper for various conditions;

Fig. 14 are charts showing the somatic evoked potentials (SEPs) measured over

a square area;

Figs. 15 illustrates charts showing the outputs from a 600 Hz signal for a piglet; Figs. 16 illustrates charts showing recordings of SEF outside the brain and intracortical SEP;

Fig. 17 are charts showing that the Kyna-insensitive component was localized

within layer IV and that the presynaptic component was generated by the thalamocortical terminals within the cortex;

Fig. 18 is a cross-sectional side view of a headrest according to one embodiment

of the invention;

Fig. 19 is a chart illustrating the cancellation of the ambient earth magnetic field

changes achieved in the frequency range below about 5 Hz; Fig. 20 is a chart showing the noise cancellation for the line frequency noise using

8 reference channels;

Fig. 21 is a pictorial view of another embodiment of an MEG system, which is

constructed in accordance with certain embodiments of the present invention;

Fig. 22 is a side elevational view of the system of Fig. 21 , illustrating it with portions thereof partially broken away for illustration purposes;

Fig. 23 is an enlarged-scale sectional view of the system of Fig. 21 , illustrating the

headrest assembly and dewar;

Fig. 24 is an enlarged side elevational sectional view of the headrest assembly of

the system of Fig. 21; Fig. 25 is an enlarged sectional view of the headrest assembly of the system of

Fig. 21 , similar to Fig. 24 except taken at a different sectional plane;

Fig. 26 is an enlarged-scale pictorial view of the array of sensors of the headrest assembly of the system of Fig. 21, illustrating the sensors in their relative positions; Fig. 27 is an enlarged face view of the headrest assembly of the system of Fig. 21;

Fig. 28 is an enlarged face view of the rear surface of the headrest assembly of

Fig. 27; and

Fig. 29 is an enlarged sectional side elevational view of the headrest assembly

and its supporting structure.

DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

According to certain embodiments of the present invention, there is provided a

magnetoencephalography system and method employing a portable cart having a

SQUID dewar mounted in an inverted manner thereon, and having a headrest assembly

mounted on the cart for supporting the head of a patient and forming a portion of the

dewar. The headrest assembly includes an array of magnetic sensors of the SQUID

dewar for responding to electrical activity of the brain of the head. The dewar is inverted

in that its sensors are disposed above its reservoir.

According to certain embodiments of the present invention, there is provided a

mounting arrangement for a magnetoencephalography (MEG) system headrest

assembly forming a portion of a SQUID dewar and having a fixed headrest and an array

of sensors, wherein a sensor array plate positions the sensors relative to the headset. A

plurality of first rods interconnecting the array plate and the movable mounting member.

A plurality of second rods are fixed at one of their ends relative to the dewar and are

connected at their opposite ends to the movable mounting member. Each one of the

first and second rods is composed of material expandable and contractible with changes

in temperature, whereby the movable mounting member tends to be moved in one

direction toward or away from the sensor array plate, and tends to be moved in an opposite direction away from or toward the array plate, resulting in temperature changes affecting the first and second rods, so that the sensor array plate and its sensors

maintain a substantially constant spacing between the sensors and the headrest with

changes in temperature. A plurality of second rods are fixed at one of their ends relative to the dewar and are connected at their opposite Each one of the rods is composed of

material expandible and contractible with changes in temperature, whereby the movable mounting member tends to be moved in one direction toward or away from the sensor

array plate, and tends to be moved in an opposite direction away from or toward the

array plate resulting in temperature changes affecting the first and second rods, so that the sensor array plate and its sensors maintain a substantially constant spacing between

the sensors and headrest with changes in temperature.

According to the disclosed embodiment of the invention, the first and second rods

are each composed of quartz material.

According to other features of the invention as disclosed herein, the sensor array plate is supported from below by the first and second rods. Additionally, as disclosed

herein, a movable is positioned below the sensor array plate and the second rods extend

upwardly therefrom. Additionally, according to the disclosed embodiment of the invention, the headrest is rigidly attached to the dewar.

MODULAR SENSOR MEG SYSTEM Referring now to the drawing and more particularly to Figs. 1 A and 1 B thereof, the

disclosed embodiments of the present invention relates to a high-resolution magnetoencephalography (MEG) systemlO for evaluating neurological impairments of

preterm and term babies, for example. The system 10 provides a non-invasive neurodiagnostic tool that may complement electroencephalography (EEG) in assessing possible neurological dysfunctions and brain development in neonates through its

capability to detect electrophysiological functions in focal areas of the cortex in real time with or preferably without signal averaging.

The system 10 is a portable, non-invasive MEG system that can be used next to a

crib 12 of any neonatal care unit without a cumbersome magnetically shielded room (not

shown). The system 10 includes a cart 14 which may be the size and shape of an

examination table with a headrest assembly 16 for receiving the head of a patient (not shown). Desirable spatial resolution and sensitivity may be provided by a closely- spaced evenly-distributed array (e.g., 19 x 4-channel modules) of superconducting MEG

sensors 18 housed below the outer surface of a headrest 21 (Fig. 1 B) of the headrest

assembly 16. For example, the sensors may be housed between about 1 mm and about

3 mm below the outer surface. The sensors may be protected against radio frequency (rf) noise. The entire system is light enough to be portable, and the cart 14 includes

wheels such as wheels 23 and 25 for rollably supporting the cart on the ground.

A dewar 27 of a superconducting quantum interference device (SQUID) is

mounted in an inverted manner on the cart 14. A patient bed or cushion 29 is mounted on the cart 14 adjacent to the headrest assembly 16 for supporting the body of the

patient with his or her head supported by the headrest.

The SQUID dewar 27 includes a liquid helium reservoir 32 and a fill port 34. A

SQUID phase lock loop electronic circuits and routers unit 36 control the SQUID

functions and are used for data acquisition. The unit 36 is mounted on cart 14. A

computer and power supply unit 38 is mounted at the rear end of the cart 14. A monitor and keyboard unit 41 are mounted above the unit 38 and communicate electrically

therewith. A short sensor distance combined with improved sensor noise provide

unprecedented sensitivity and spatial resolution for infant studies. The system 10 may

be about one order of magnitude better in sensitivity than the conventional whole-head

MEG sensors (e.g. Ahonen et al., 1992; Buchanan et al., 1994). Its sensitivity may be sufficiently high to measure not only spontaneous neuronal activity, but also evoked

activity of the cortex of the newborns in real time preferably without signal averaging. Its

spatial resolution system 10 will be greater by a factor of about four in comparison to the

existing whole-head MEG sensors.

The system 10 takes advantage of the fact that the infant's scalp and skull are

thin. This make it possible to measure MEG signals at a distance of only between about 5 mm and about 6 mm from the brain surface. This short distance results in a very large

amplitude of MEG signals from the newborns, since the magnetic field is inversely

proportional to the square of the distance. The short distance and a high density of

detectors also result in high spatial resolution. It has been determined that a 4-channel module with a noise level less than 10

fTΛ/Hz for detection coils with a diameter of about 6 mm can be built. Further, the

headrest 21 can have a thickness of about 1.0 mm or only slightly greater and is safe to

use for the system 10 (i.e., that holds the vacuum without breakage) can be constructed. The sensitivity of the system 10 should be high enough to clearly detect evoked cortical

activity preferably without signal averaging.

In certain embodiments of the invention, the MEG sensors are housed in a

vacuum section just below the headrest assembly 16. The wall of the headrest is thin

(about 1 mm or only slightly greater) so that the detection coils of the sensors can be

placed as close to the head as possible (~2 mm). The sensor array 18 of one embodiment of the system 10, includes of 19

modules, each module having 4 channels of sensors. It will be understood hereinafter described in greater detail, the sensors can be arranged in clusters in accordance with

another embodiment of the invention. Such modules can be fabricated with a noise level

of less than 10 fϊV Hz for sensor pickup coils with a diameter of 6 mm. This is possible

even though the cross sectional area of the coils is about 10 times smaller than those of

the conventional whole-head sensors.

The sensitivity of the system 10 is sufficiently high to clearly detect evoked cortical

activity without signal averaging. A test was carried out by measuring the somatic

evoked magnetic fields (SEFs) in 1-7 month old infants with a microSQUID (not shown)

which was similar to the system 10 in that it has a 4-channel module in the vacuum

space just below the tail section of a conventionally oriented dewar. The distance between the pickup coils and the outer dewar wall surface was very short (about 1.2

mm) and comparable to the distance for the system 10. The noise level of the system

10 may be about 5 to about 6 times better than that of the prior known similar MEG

systems. Thus, one can extrapolate from the SEFs measured with the system 10 to infer whether evoked cortical responses can be indeed measured without signal averaging using the system 10. In one embodiment of the invention, clear signals were

measured non-invasively by averaging 16 responses to vibratory stimuli and 36 responses

to air puffs applied to the tip of the index finger. Extrapolating from these results, it may be concluded that the system 10 is able to clearly detect such SEFs without signal averaging, since the system 10 requires between about 25 and about 36 times less averaging than the prior known similar MEG systems to obtain signals with comparable signal-to-noise ratios. The system 10 is the size of an ordinary examination table in one embodiment of the invention. The system 10 itself is provided the cart 14 with the mattress or bed 29

on top thereof, adjacent to the headrest. The acquisition of brain signal is relatively

rapid, since there is no need to attach electrodes, as in the case, for example, of an

EEG. The measurements of MEG signals can start immediately after placing the baby on the bed 29 and the head in the headrest assembly 16. For conventional EEG,

placing electrodes on the scalp is time consuming and often troublesome since the baby may easily resist. The baby may wake up if not sedated. This practical problem limits

the number of electrodes to be used in any diagnosis, thereby severely limiting the

inference that can be made regarding the nature of brain abnormality.

The MEG system 10 is also able to function in clinical rooms without magnetic

shielding. An ideal system should function without interference from the ambient

magnetic field, line frequency and radio frequency noises, for example. The system 10

may be equipped with SQUID control electronics with, for example, an effective dynamic range of about 32 bits that resolve magnetic fields between about 10 μT and < about 1

fT. It may also have a fast slew rate that can follow magnetic field changes as fast as about 10 μT/ms which is fast enough to follow changes in the line frequency noise

without loosing the lock on the flux-locked feedback loop. This fast slew rate enables

the system 10 to maintain the SQUIDs operating continuously in the midst of low frequency magnetic field changes and line frequency noises. The short-line baseline

gradiometers and the reference channels enable the low frequency and 60 Hz noise to

be cancelled with a suppression rate of between about 30 dB and about 90 dB. Thus,

the system 10 may operate in unshielded environments. The above features make the system 10 useful in an ordinary clinical setting. In

addition to these features, the MEG system 10 may have a sufficiently high level of

sensitivity and spatial resolution to provide new information for certain applications. The

system 10 may satisfy this essential requirement by taking advantage of several unique

features of the head of infants. First, the skull and scalp of a newborn are quite thin.

The human skull at the age of 6 months after birth has an average thickness of about

2.5 mm (minimum of about .3 mm, maximum of about 3.7 mm) for girls and about 2.7

mm (minimum of about 1.7 mm, maximum of about 3.8 mm) for boys (Hansman, 1966).

Extrapolating from their normative data in connection with certain embodiments of the

invention, the skull should be between about 1.7 and about 2.0 mm thick at birth. The

scalp is also about 1 mm thick in the first several months of age. Thus, MEG sensing

coils can be placed as close as between about 5 and about 6 mm from the cortical

surface when the MEG system 10 is built with about a 2 mm distance between the

outer surface of the pillowcase and the sensing coils. The system 10 may be thus

capable of measuring MEG signals at a distance of about 5 mm as opposed to between

about 25 to about 30 mm for the conventional whole-head MEG instruments. Thus, the

measurement distance for a cortical source 3 mm below the surface of the brain would

be about 8 mm and about 30 mm for the system 10 and a conventional whole-head

MEG system. This implies that the signal may be more than 10 times stronger when

measured with the system 10. Therefore, it may be possible to monitor cortical activity

in real time without signal averaging. Monitoring cortical activity at a distance of about 5

mm also increases spatial resolution. The sensing coils are tightly packed in the system

10 to maximize the spatial resolution. The spatial resolution of the system 10 is about

four times higher than that of the conventional whole-head MEG systems. For an example of a whole-head MEG system, reference may be made to U.S. patent

6,023,633, which is incorporated herein by reference. All sensor coils are assembled

below the headrest, so that there is no need to position each sensor precisely as it would

be required by EEG if one were to carry out a quantitative EEG analysis. The high-

density packing of the sensors in the system 10 make it possible to delineate the

abnormal cortical region such as the bilateral strip of cortical tissue along the anterior-

posterior direction expected in the case of parasagittal cerebral injury typical of term

infants who have suffered a temporary ischemia or anoxia.

Certain embodiments of the system may be capable of measuring cortical activity

as if its sensing coils are placed a few millimeters above the cortical surface without the

intervening scalp and skull, that is as if the scalp and skull are removed and the sensors

lie very close to the exposed cortical surface. The magnetic field above the head is

essentially the same as the field present at the cortex except for an attenuation of signal

amplitude and spread of the spatial distribution of the magnetic field merely due to the

slightly larger distance of measurement. This means that an MEG signal above the

scalp should be quite similar in information content to the signal just above the cortex.

MEG signals are transparent to the scalp and skull, unlike EEG, even in the presence of

skull defects created by the fontanels and sutures. It has been argued that the skull is

"transparent" to MEG signals (Kaufman et al., 1981) on the basis of theoretical results

obtained by Geselowitz and Grynszpan (Geselowitz, 1970; Grynszpan and Geselowitz,

1973). This conclusion is supported by simulations studies (Hamalainen and Sarvas,

1989), by measurements of MEG signals outside the head of a cadaver with a hole in

the skull (Barth et al., 1986) and by a careful comparison of the topography of the somatic evoked magnetic fields before and after a hole is introduced in the skull in an in

vivo piglet study (Okada et al., 1999b, see Phase I Final Report).

In comparison, EEG signals may be significantly distorted by skull defects that are

unique to the human neonates. The fontanels are present at the midline junctions of the

bregma and lambda. The skull is not present within the fontanels; instead the brain is

protected by a thick dura filling the windows. They are small during the delivery, but

become larger in the first several months, up to between about 3 cm and about 4 cm

along the coronal suture, and then eventually they close. The anterior fontanel may be

large enough to admit an adult's thumb. The unclosed sutures can be quite wide near

the fontanels. The mean width of the coronal and lambdoidal sutures at their

midpositions is 3-4 mm for infants between 0 and about 60 days after birth (Eramie and

Ringertz, 1976). In abnormal cases such as hydrocephalous, the sutures may change

its width with the development of the disease and become as wide as 10 mm or more

(Eramie and Ringertz, 1976). Moreover, the sutures do not close for many years

(Hansman, 1966). The earliest age for complete closing of the sagittal and coronal

sutures are 6 and 1 years, respectively. Thus, EEG signals may be profoundly affected

by the fontanels and sutures since they create paths of low conductivity for the volume

currents in the brain and funnels the currents through these openings in the skull.

It might be argued that the skull defects are not a disadvantage for EEG, but on

the contrary, are an advantage. In diagnosing seizures the breech provided by the

fontanels improves the sensitivity of the EEG. However, the skull defects may obscure

the asymmetry of the signals, especially when the generator is deep, making it difficult to

determine the epileptiform tissue when it can not be easily visualized by CT or MRl. The conductivity of the skull is also expected to change with age and across individuals. The skull thickness increases rapidly within the first three years of age from

about 2 mm at birth for term newborns to about 5 mm at 3 years of age for boys, then the growth slows down (Hansman, 1966). The skull thickness reaches a mean of about

8.3 mm and about 9.5 mm for 25 year-old women and men, respectively. These

changes in skull thickness are associated with thickening of the dense, poorly-

conducting inner and outer bony tables of the skull relative to the spongy middle layer containing blood and with a decrease in effective conductivity of the skull with age. Also,

important is the variability in skull thickness. The 10th-90th percentiles are 2.4-4.6 mm

and 3.0-4.9 mm for 1-1/2 year old girls and boys. That is, the range is 50-60% of the

means. At the age of 25, the 10th-90th percentile range is 40-50% of the means for

women and men.

EEG signals may be distorted not only by skull defects, but also by the brain-skull

and scalp-air boundaries of EEG waveforms in certain circumstances. Goff et al. (1978) have shown that the attenuation of scalp potential is highest for focal cortical sources and lower for extended cortical and subcortical sources. The attenuation of potential

may be as much as about 50 times greater for a 6° cortical source compared to a focal source at the center of the brain and as much as about 100 times greater for such a

shallow focal source compared to extended sources subtending a solid angle between

about 72° and about 180° regardless of depth. This large variation, depending on source

depth and extent, implies that the EEG signals on the scalp would be most likely different or deformed in comparison to the signals on the cortex. The components due

to focal cortical sources may be small relative to deeper sources and thus some of the cortical components may be difficult to be identified or distinguished, being

overshadowed by signals from extended cortical or deeper subcortical sources.

In summary, the MEG system 10 assesses neonatal brain functions and serves as a useful non-invasive clinical tool for monitoring physiological functions of the pre- term and full-term neonates born with possible neurological disorders.

Figs. 2 and 3 show one embodiment of the headrest assembly 16 of a system 10

configured as a contoured semi-ovoid having a honey-comb shaped rear wall. The

honey-comb rear wall design enables the placement of the MEG detection sensor coils at a distance of about 1.5 mm or 2 mm (Fig. 2B) from the outer surface of the headrest

21 and, at the same time, provides a sufficient strength to protect the headrest 21

against the vacuum. The space where the sensor detection coils and SQUID dewar are

housed may be in vacuum to provide thermal insulation.

The sensor array of sensors 18 in one embodiment of the system 10 consists of

19 clusters of 4 sensors, each arranged as shown in Fig. 3, such that there is a reduced amount or minimum of space between individual sensors 18, given the honeycomb

structure. Such modules may be built with a noise level of less than 10 TV I Hz. The preferred embodiment of the headrest uses a honey-comb rear-wall design with

individual circular or elliptical windows or recesses (Fig. 3) for the 19 modules, each module (or cluster) including 4 channels of sensing coils. The primary advantage of

using individual windows or wells is the ability to achieve close spacing to the head while

providing strength to withstand against vacuum. In this regard, the sensors 18 are positioned within the recesses in the rear wall where the headrest wall is the thinnest.

The headrest assembly 16 was tested to determine whether the individual

windows or recesses in the honey comb rear wall design can withstand against the vacuum (one atmosphere pressure) of the dewar 27. Extending the theoretical results,

the expected deflection was calculated at the center of a G-10 fiberglass window or

recess against the differential vacuum pressure of one atmosphere as a function of

window or recess diameter and thickness. The deflection was calculated using a

Mathcad routine based on Roark's formula for deflection (Roark and Young, 1975). A

specific case of flat circular plate with fixed edges and uniformly distributed pressure was

exploited. Young's modulus (E) of 2 x 10⁶ was used for G-10. Table 1 shows the

results:

Table 1. Theoretical deflection at center of G-10

The deflection was less than about 100 μm for a 1.0 mm-thick window with a

about 30 mm were chosen to be slightly larger than the diameter needed to

accommodate a 20-mm diameter module. These theoretical results were verified

empirically. We constructed a 28-mm diameter G-10 window of varying thicknesses,

fixed the window on top of a fiberglass cylinder using epoxy seal and then evacuated the

inside of the cylinder. The deflection at the center of the window was measured with a

micrometer. Table 2 shows the results: Table 2. Measured deflection at center of G- 10 window

The empirical results were quite close to the predicted values shown in Table 1.

Interpolating from Table 2, the deflection was less than about 100 μm for a 1.0-mm thick window. The vacuum was held by the window even for a 0.4-mm thick window. Based

on these results, the honey comb rear wall design with a wall thickness of between about

1.0 mm and about 1.5 mm appears to be safe to use for the system 10.

The safety of the window was evaluated with yet another test. A 25-mιm diameter

chrome-alloy ball bearing was dropped from varying heights onto the center of selected

28-mm diameter windows. The windows were epoxied onto the vacuum test fixture and a vacuum gauge measured the integrity of the window during impact. Table 3

summarizes the results:

The results of this drop test appears to demonstrate that a G-10 fiberglass

window can withstand a significant impact even for a wall thickness of about 1 mm. The

1-mm-thick window did not show any visible damage nor leak even when the large steel

ball was dropped from the height of about 60 cm. This second test, thus, reinforces the

conclusion that a honey comb design with a wall thickness of between about 1.0 and

about 1.5 mm appears to be safe to use for the system 10.

In addition to testing individual windows, the safety of an entire headrest 21 was

tested. For the purpose of this safety evaluation, a headrest with a uniform wall

thickness was constructed and determined the deflection of the center of the headrest

and its ability to withstand against one atmospheric pressure was determined. The

baby's head was modeled as an ellipsoidal volume with a radius of curvature of about 6

cm along the coronal section and 8 cm along the sagittal section, using a standard

reference for the head sizes (Lusted and Keats, 1978). The negative mold for the

headrest was then carefully made with gelucel wood, sealed with polyurethane varnish

and then heavy carnuba wax was applied as a mold release prior to applying the

fiberglass. Polyester resin and glass cloth were laminated directly into the negative

mold. In manufacturing the system 10, a positive mold of the representative baby's head

may be made from the negative mold and the headrest may be made from this positive

mold to ease removal of the cast form.

Each one of the sensors 18 is a first-order asymmetric, axial superconducting

gradiometer. The sensors 18 are arranged in clusters of 4 separated by the honeycomb

rear wall of the window or recess (Fig. 3), although the result is substantially equal

spacing between sensors. The expected noise level for the gradiometers with a pickup coil diameter of about 6 mm may be about 10 TV/ Hz or better. Such a module has been fabricated and determined its noise level has been determined.

Fig. 5 shows the pickup coils, which are about 6 mm in diameter in one

embodiment, since the distance between the pickup coils and the cortical surface will be

about 6 mm. This diameter is optimal for this measurement distance in considering

spatial resolution and sensitivity.

To design a 4-channel module, it may be necessary to calculate the crosstalk

between coils for some applications. This was done as a function of coil separation.

The calculations demonstrated that the coils in the 4-channel module had to be spaced

diagonally by about 12 mm in order to maintain less than about 2 % crosstalk. Based on

the noise and the crosstalk considerations a 4-channel module was designed, as shown

in Figs. 5 and 6.

Figs. 7 and 8 show the noise spectra for the two channels. The noise spectra were quite clean with an elbow frequency (where the 1/f noise starts) of about 1 Hz. Based on these results, it appears that a 4-channel module can be constructed with a

noise level of 10 TV/ Hz.

A study of SEFs in human infants using the microSQUID was carried out. The

purpose was to show by extrapolation that it should be possible to measure cortical evoked activity without signal averaging using the system 10.

Figure 9 is a graphical representation of the results of the study and show representative samples of the SEFs produced by piezoelectric vibratory stimulations

(left) and SEFs produced by air puff stimulations (right). The data with vibratory

stimulations were obtained from 9 sessions (9 subjects) and those with airpuffs were obtained from 8 successful sessions (4 subjects). For both stimuli, the SEF reversed its polarity near C3, indicating that its generator was located in the somatosensory cortex

below C3. The SEF was stronger for the vibratory stimuli than for the airpuffs, but the waveforms were similar. The initial component was directed into the head over the

upper region of the measurement area, whereas it was directed out of the head over the lower part, indicating that the underlying current was directed from the deep layer to the

superficial layers of area 3b. The latency delay of this initial component for the air puff

stimulation relative to the vibratory stimulation is due to the delay in the arrival of the

compressed air to the finger via the tubing. The timing of the air puff stimulation,

measured with a pressure transducer at the end of the tube, shows a delay of about 35 ms in the start of the pressure and a further delay of about 85 ms before the pressure

reached the maximum. The latency delay of the initial component is approximately 35

ms indicating that the initial component was triggered the very early phase of the

pressure change.

The SEFs obtained as a result of the study strongly support the prediction that similar evoked cortical activity with a comparable signal-to-noise ration (SNR) can be

seen in real time using the system 10. The SEFs for airpuffs are averages of 36 epochs,

whereas those for vibratory stimulation are averages of 16 epochs. Therefore, it

appears that it is possible to obtain SEFs of comparable quality in single trials with the

system 10, even for airpuffs, since its noise level is expected to be about 6 times less than that of a conventional microSQUID. In this regard, the SEFs shown in Fig. 10 are

produced by a vibratory stimulation as a function of number of epochs in the average. It is clear that reliable SEFs can be seen even after averaging less than 25 epochs, after

as little as 4 epochs. The bandwidth of the recordings was 50 Hz, passing between 1 Hz

and 50 Hz. The system 10 enables a study to be carried out by simply placing the baby's

head on the headrest assembly 16, instead of placing the detector above the head as

was the case for the conventional microSQUID. This inverted design of the dewar 27 of

the system 10 provides a sense of safety to the parents who would be present at such a

study. Parents would tend to express concern after seeing the baby's head being

sandwiched between a conventional detector and the bed. The coverage expected with

the 76-channel system 10 tends to speed up the study, since the measurement time is

very limited when no sedative is used. The set up time for the measurements is reduced

or minimal with the system 10 since no electrodes are required to be placed on the scalp

unlike EEG. This also greatly increases the usefulness of the system 10 for routine

measurements.

The system 10 may well be very useful for neonatal brain assessment. The

results of testing indicate that: (a) an MEG system has little or no affect by the skull (b)

EEG is strongly affected by a hole in the skull mimicking the anterior fontanel in the

infants, (c) EEG signals are strongly distorted as a function of depth of the active tissue,

and (d) the system 10 may well be capable of providing new information about the

physiology of the thalamocortical fibers and cortical neurons in certain circumstances.

Okada et al. (1999b) have shown that the SEF measured on a plane above the

skull of the piglet is virtually the same in waveform and spatial distribution with and

without the skull (Fig. 11). The SEFs measured in the skull-on (wave forms A), skull-off

(wave forms B), and skull-on again (wave forms C) conditions could be superimposed

with no clearly visible differences (wave forms D). Little, if any distortion was seen when

the SEF was measured with the skull intact and after the dorsal portion of the skull was

removed (Okada et al., 1999a). A quantitative evaluation of the similarity has, however, shown that the skull does influence the external MEG signal as the generator becomes

deeper, due to the fact that the skull is not spherical. This result confirmed a theoretical

result by Hamalainen and Sarvas (1989) showing that the MEG signal outside the head

calculated with a boundary element model is the same regardless of whether the scalp and skull are present. It also confirms an experimental finding by Barth et al. (1986)

showing that a large hole in the skull of a human cadaver does not distort MEG signals

produced by an artificial source embedded in the cranium.

There does not appear to be any study which explicitly demonstrated a distortion

in the waveform and spatial pattern of EEG signals caused by a hole such as one mimicking the fontanel in human infants. The large size of cranium in the piglet preparation used in Dr. Okada's laboratory enables one to test this question empirically.

Figure 12 shows an outline (dashed square) of the SEP (somatic evoked potential)

measurement area on the skull with a square hole (12 mm x 12 mm) over the left

hemisphere. The hole was over the cortical area generating the early responses in the

primary somatosensory cortex produced by snout stimulation. The SEP was mapped

with a 16-channel electrode array placed on a 0.9% NaCI saline-soaked filter paper

covering the entire measurement area and mimicking the scalp that was removed. The

SEP pattern was measured in three conditions differing widely in the electrical conductivity of the hole, so that the distortion can be measured as a function of

conductivity. The hole was filled with air r= 0), isotonic 3% agar containing 330

milliequivalent of sucrose (fr~ 0.01 S/m close to the conductivity of the skull), with

isotonic 3% agar containing 0.9% NaCI (<r^~1.28 S/m). Under these conditions, the SEPs (bandwidth: 1- 200 Hz. 60 epochs/ave), especially their early components, were large in sucrose- and saline-agar compared to the air conditions.

The distortion due to conductivity differences in the hole is clearly revealed by the difference map shown in Fig. 13A (each trace bandwidth: 5-200 Hz, 60 epochs/ave). The differences were large between the sucrose and air conditions where the

conductivity of the sucrose-agar should be close to the conductivity of, in this case about

a 2.5 mm thick, skull. The differences were also quite reproducible as seen by the

similarity in the sucrose1-air and sucrose2-air different maps.

The Laplacian transformation is becoming more commonly used in deblurring the scalp EEG pattern (Gevins et al., 1994, 1999; Le et al., 1994; Nunez et al., 1994). This

method is used to estimate the current emerging or entering the scalp along the direction perpendicular to the surface as a result of neuronal activity in the brain. This current is

conventionally estimated by solving the Poisson equation. In practice, the current Im is

estimated from a discrete version of this equation: Im 4V(xO,yO)-V(dx,yO)-V(-dx,yO)- V(x0,dy)-V(x0,-dy), when the potential is measured at five positions centered at position

x=x0 and y=y0. The Laplacian estimate of currents emerging through the filter paper

(mimicking the scalp) is shown for the three conditions in Fig. 13B. The calibration is

based on an electrode separation (dx=dy) of 4 mm and a conductivity of 0.016

Siemens/m for the sucrose-agar and 1.27 Siemens/m for the saline-agar. Note that the current magnitudes are much larger over the saline agar. This result clearly

demonstrates that currents leak through a hole and distort the EEG pattern on the scalp when such a hole is above an active area of the cortex. In sum, these results empirically demonstrate that EEG signals are distorted by a hole in the skull, suggesting that the skull defects such as the fontanels and sutures may profoundly distort EEG signals in infants.

The following study compared the SEPs measured on the dura and on the scalp

and, similarly, the SEFs measured on the dura and scalp in order to determine whether

these signals seen outside the scalp are similar to those over the cortex. Goff et al.

(1978) showed that the potentials due to focal cortical generators are more attenuated than those due to extended cortical or deeper sources when the potential is measured

on the scalp. This implies that the waveform of the SEP on the cortex or dura should be

distorted when it is measured on the scalp. The "transparency" of MEG, on the other

hand, implies that the SEF on the scalp should be similar in waveform to that on the

cortex or dura.

These experiments were carried out on piglets of less than 1 week of age (1-6 days) as a neonatal model of human newborns. The skull of these piglets are 0.5 -1.5

mm in thickness over the dorsal portion of the cranium. The scalp is about 1.5 mm in

thickness. They do not possess fontanels, but the sutures are still present and the

cranial bones are loosely attached. Figure 14 shows the SEPs measured over a square

area (indicated by the solid line) and the SEFs measured over the dashed area, both roughly centered over the active area in SI responsible for early cortical responses. The

snout was electrically stimulated and the SEPs were measured first on the scalp, then

with the scalp and skull removed and finally on the scalp again in order to control for possible changes in the physiological condition of the animal. The procedure was

repeated for SEF measurements. The scalp and skull were cut before the experiment, then the skull was replaced and the scalp was attached to the intact skin with a suture.

The suture was removed for dura measurements and then the scalp was sutured again. The combined thickness of the skull and scalp was 3 mm. It can be seen that the SEP

and SEF were very similar in the scalp 1 and scalp 2 conditions, indicating the animal

was in stable physiological condition and other extraneous factors did not contaminate

the results (signal bandwidth = 1-200 Hz, 30 and 60 epochs/ave for SEF and SEP,

respectively).

The inset in Fig. 14 labeled "scalp and dura EEG" compares the SEP at its

potential extremum for the early cortical component (indicated by an open circle) in the

scalpl , dura and scalp2 conditions. The solid curve in (a) is the dura SEP and the two

dashed curves are the scalp SEPs. The peak amplitude of the first component of the

scalp SEP was magnified to match that of the SEP on the dura as shown in (b). Clearly,

the later components of the magnified scalp SEP are larger than the corresponding

components of the SEP on the dura, with a good reproducibility for the two scalp

conditions. Thus, the attenuation ratios are different for different components of the SEP

and thus the scalp SEP is distorted in waveform in comparison with the dura SEP.

The same comparison was made for the SEFs. The SEF distribution on the dura

was more compact than the distribution over the scalp due to the shorter measurement

distance, just as was the case for the SEPs. Taking this into account, the waveforms

were compared at the field extremum of the earliest component of the SEF in the three

conditions. The inset in Fig. 14 labeled "scalp and dura MEG" compares the waveforms

at the location indicated by a circle in the three conditions. In (a), the scalp SEFs (two

dashed curves) were weaker than the dura SEF (solid curve), but they could be scaled

by a constant (see b), again by enlarging the scalp SEF to match the peak of its earliest

component with that of the dura SEF. Thus, the SEF waveforms were comparable on

the dura and scalp. In sum, the results of this study indicate that it may be possible to measure SEF over the scalp as if the scalp and skull were absent, whereas the SEP on the dura may be distorted on the scalp.

The above result implies that it should be possible to non-invasively measure

cortical activity with MEG as if the skull and scalp were removed and the sensors are

practically placed on the cortex if the skull and scalp are thin as it is the case for

neonates and furthermore if the sensors can be placed very close to the scalp. This suggests that it may be possible to non-invasively measure cortical activity as if we had

electrocorticographic sensors were positioned on the cortex.

It has been suggested that the high-frequency signal, the so-called 600 Hz signal,

may reveal spike activity (Curio et al., 1994a, b; Hashimoto et al., 1996a; Haueisen et al., 2000a, b). This study has shown that it is possible to detect the 600 Hz signal and determine the origin of this signal in the piglet model using the microSQUID. Figures

15A-D show that the 600 Hz signal from the SI of the piglets has properties very similar

to those found in the human SEP and SEF. The SEF was first scanned over the SI and

then the 4-channel detector was placed directly above the generator of the first cortical

response (marked by x in Fig. 15A). In some experiments, the SEP within the cortex

was measured simultaneously or sequentially with the SEF in the same animals using a glass micropipette or a 16-channel microelectrode array. In others, SEPs were

measured separately. Fig. 15B shows the wideband (1 Hz - 3,000 Hz) signal at locations SQ2 and SQ4 along with the narrowband (416-2,083Hz) SEF, the difference wave between the SEFs measured at SQ2 and SQ4 and the power of the difference

wave (square of the difference wave). The amplitude spectrum of the wideband signal (Fig. 15C) was very similar to that found in the humans with a clear peak around 600 Hz

(Curio et al., 1994b; Hashimoto et al., 1996a). The SNR of this signal compared to the noise level during the prestimulus period was 10:1. Also in agreement with human

results (Emerson et al., 1988; Yamada et al., 1988; Hashimoto, 1996a), the amplitude of

the first SEF component corresponding to the human N20m increased while the

amplitude of the 600 Hz decreased with an increase in depth of sleep induced by an

increase in the level of the anesthetics (ketamine/xylazine) (Fig. 15D).

Signals with the quality shown in Figs. 15A-D were obtained from the humans

with an average over about 1,500-5,000 epochs (Curio et al., 1994b, Hashimoto et al.,

1996a). The signals are based on average of 3,000 epochs, even though the

measurement distance was about 8 mm in the present study and probably 40 mm in the

human studies. If the source strength was the same in the humans and piglets, the

signal should be about 25 times ((40/8)²) stronger. The signals in humans are typically

10-30 fT peak-to-peak. In the present study the signal was as much as 400 fT as

compared to the expected value of 250-450 fT. Thus, the magnitudes do scale. The test

results indicate that the system 10 is 5-6 times more quiet than a conventional

microSQUID and thus there is needed about 25 times less average or about 100 epochs

to obtain signals of comparable quality in the piglets. This implies that it should be

possible to measure this signal from infants by averaging about several hundred signals

since the scalp and skull add to the distance of measurement.

Taking advantage of the animal model, the origin of this 600 Hz signal was also

determined. Simultaneous recordings of SEF outside the brain and intracortical SEP

revealed that the narrowband signals measured with MEG were very similar to the

extracellular intracortical activity (Fig. 16A). This indicated that the 600 Hz signal was

generated in the cortex. Based on human studies, it has been proposed that the

generator of this 600 Hz signal may be the thalamocortical axonal terminals (Gobbele et al., 1998), inhibitory interneurons in the cortex (Hashimoto et al, 1996a; Mackert et al.,

2000) or excitatory cortical neurons. Kynurenic acid (Kyna, 20 mM), a non-specific

antagonist of excitatory amino acid neurotransmitters, was used to separate the

presynaptic and postsynaptic components of the 600 Hz signal. The SEF and

intracortical SEP were measured simultaneously with the microSQUID and a 16-channel

electrode array fixed in place in the cortex during the control condition without Kyna (Fig.

16A, control). This showed that the SEF power consisted of two components, one

around 8 ms and the other between 10-15 ms post-stimulus. Application of Kyna with a

pair of glass micropipettes in the projection area of the snout greatly reduced the second

component, whereas the first component was intact (Fig. 16B). This second component

showed partial recovery during the washout phase (Fig. 16C). Fig. 16D shows the

selective effects of Kyna on the first component of the simultaneously measured SEF

and SEP. Thus, there are Kyna-insensitive and sensitive components which indicate

that there are pre- and post-synaptic contributions to the high-frequency signal.

Fig. 17, left, shows that the Kyna-insensitive component was localized within layer

IV which is the receiving area for specific thalamocortical afferents. A detailed analysis

of the presynaptic component, Fig. 17, right, shows that this component was generated

by the thalamocortical terminals within the cortex. The laminar profiles within the control

and Kyna conditions showed an initial wave, starting about 6 ms post-stimulus, of

extracellular negativity that were strongest near the white matter. This wave did not

reverse polarity within the cortex. Then, two components (at time points 2 and 3)

showing polarity reversal appeared at 7.2-7.9 ms. The extracellular potential was

negative in layer IV (~1 ,000-1 ,200μm) and positive in the superficial and deeper layers,

indicating that it was generated by the thalamocortical terminals in the receiving layer. A trigeminal brainstem study showed that the snout stimulation produces activity in the

trigeminal nuclei with a shortest latency of about 4.5 ms and that the impulses were

carried by the fast, myelinated Aβ fibers with a conduction velocity of 32-42 m/sec. This

implies that the thalamocortical volley may arrive in the cortex as early as 7.3 ms, taking

into account one synaptic delay in the thalamus. Thus, the Kyna-insensitive component

at around 8 ms appears to be of thalamocortical origin on this ground as well. About 1.1

ms later, there was a large Kyna-sensitive component in layer III in the control condition.

The laminar profile at its peak (time point 4) is shown in Fig. 17. This is the first post¬

synaptic component produced by the cortex. Fig. 17, left, shows that this post-synaptic

component was produced in layers II-VI with a delay between the activity in layer lll/IV

and layer V/VI. Also, importantly, Fig. 17, left, shows that this post-synaptic component

became larger 3-4 hrs after the injection of Kyna, indicating that this component showed

hyper-excitability. This suggests that it was generated by excitatory cortical neurons due

to partial blocking of inhibitory neurons by Kyna. It has been thought for a long time that

the detection of synchronize population spikes would be extremely improbable based on

the careful work of Humphrey (1968a, b) who has shown that the antidromically

generated action potentials contribute little to the cortical surface record. However, it

appears possible from outside the brain to detect axonal spikes from the thalamocortical

fibers and synchronized populations spikes produced by cortical neurons using a high-

resolution MEG sensor.

The MEG sensors are housed in a cryogenic container called a dewar that stores

liquid helium. The dewar consists of two cylindrical containers. The inner container

stores a sufficient quantity of liters of liquid helium which is used to maintain the

superconducting sensors operating at the critical temperature such as about 4.2°K. The space between the two containers is in vacuum to provide thermal insulation. The inner

and outer containers may be made from a special laminated G-10 fiberglass that is constructed to prevent leakage of helium gas into the vacuum space. The dewar may

be placed on the floor of the portable cart. In one embodiment, the dewar weight may

be about 100 lb and the total bed system may be about 300 lb, so that it should be portable on wheels.

The body of the inner container may be shielded against heat radiation leak using layers of low conductivity material such as aluminum. The shielding may be installed in removable packs to enable ease of construction and rework. The gap from the inside to

the outside may be about 2 mm via independent mounts.

The top section of the dewar may be made separately from the bottom cylindrical

containers. It may be a G-10 plate with a cylinder epoxied onto the plate. The plate may

also accommodate an exhaust hole from the inner cylinder that lets helium vapor escape into the atmosphere. The exhaust hole may be sealed with a removal thermal shield to

prevent heat from leaking into the inner container. The cylinder may be machined so that

the headrest can be epoxied onto the cut surface. The headrest may have a curvature

that may accommodate the head of infants. As mentioned above the headrest may be ellipsoidal or semi-ovoid with the radii of curvature of about 6 and about 8 cm. This dimension should be sufficient to accommodate infants of up to about two years of age

(Lusted and Keats, 1978) for some applications.

As shown in Fig. 1 , the sensor pick up coils may be mounted at the top and the

associated dc-SQUIDs may be mounted at the bottom of the inner container of the dewar 27. This sensor assembly may be maintained at the superconducting temperature, by a cold heat sink attached to the bottom of the inner container. In accordance with another embodiment as shown in Fig. 18, an MEG system 44 have a

headrest assembly 46 enables the sensor array 48 to be moved adjustably relative to

headrest 51. An actuating mechanism 53 may be installed that may enable an operator

to adjust the height of the sensor as array 48 relative to the headrest 51 so that the pickup coils may be as close to the inner surface of the headrest as possible. This may

be about 2.0 mm spacing between the outer surface of the headrest and the pickup coils

when the system 10 is in use, but about 1 cm below the closest position when it is not in

use in order to conserve liquid helium.

The boil off rate for the system 44 is about 4 liters/day when it is not in use and 8

liters/day when in use according to one embodiment of the invention. Assuming the system 44 to be used 12 hours/day, a sufficient size dewar such as a 25-liter dewar may

be able to hold liquid helium for 4 days. Thus, helium transfers may need to be made twice a week for some applications.

The actuating mechanism 53 may be made as illustrated in Fig. 18. The shafts such as a shaft 50 supporting the sensor array may be spring loaded and moved up

and down by a wedge 54 that may be moved horizontally by a thermally shielded rod 52

that may protrude from the side of the dewar.

Reverting again to the system 10 of Fig. 1 , the array consists of 19 modules of 4 channels each for the disclosed embodiment. Each module may be attached to an

ellipsoidal support as shown in Fig. 3. The distance between the center of a module to the center of an adjacent module is approximately 24 mm for this embodiment.

Each module consists of 4 channels of first-order, asymmetric, axial gradiometers

in the preferred embodiment. However, other numbers of gradiometers may be

employed. The most suitable pick up coil configuration is a 12 turn, 6 mm-diameter pick up coil and a 6 turn (spaced by 1 mm), 8.49 mm-diameter cancellation coil. This is

desirable for the 3 μΦ₀Λ/Hz SQUIDS by Quantum Design, San Diego, CA, or the

SQUIDs made by Jena SQUIDs, Jena, Germany. This has a noise level of 2 μΦ₀Λ/Hz

rather than 3 μΦ₀Λ/Hz with a inductance of 0.6 μH rather than 1.8 μH. Thus, the ideal

noise (without the noise from the superinsulation and fiberglass wall) should be reduced

from 7 TV I Hz to 4.7 fT/ Hz. Furthermore, the number of turns in the gradiometer

assembly can be reduced for some applications, thereby making the fabrication of the

gradiometers coils relatively easier.

The pickup coils within and across the clusters of 4 are densely packed to

increase the spatial resolution. The coil-to-coil diagonal distance within each module is

about 12 mm for some applications. The coil-to-coil distance across the modules

between the closed coils is about 10 mm. This separation is about three times less than

the separation between channels of the latest high-density 200-300 channel whole-head

MEG systems made by the CTF Systems and 4D-Neuroimaging.

As the system 10 is designed to operate in an unshielded environment, special

precautions may be taken to provide adequate RF shielding. All cryocables (from room

temperature to the SQUID sensors) may be RF shielded. The leads from the pick up

coils may be shielded using superconducting lead tubes. The dewar superinsulation

provides partial RF shielding for the pick up coils. Each module may be RF shielded by

wrapping it with a superinsulation material.

An electronic rack may be placed in the body of the portable cart 14 below the

mattress or bed 29 (see Fig. 1). This rack houses 84 channels of SQUID control units,

76 channels for the detection coils plus three magnetometers and five first-order gradiometers to be used as reference channels for noise cancellation. All control units

may fit into one 19-inch rack-mounted card cage, sufficiently small for the entire rack

to fit comfortably within the body of the cart. The dc-SQUIDs may be connected via RF-

shielded coaxial cables to the control units.

The SQUID electronics may be powered completely by a suitable dc power

supply that may be located close to the AC power outlet of the hospital room. The use of

the dc power reduces the line frequency noise that would be sensed by the MEG

detection coils.

The system 10 must operate in electromagnetically unshielded environments

such as almost any room in a hospital. Shielded rooms are expensive, costing in some

cases between about $500K and $1M, depending on the size and level of magnetic

shielding desired. It also makes the MEG systems non-portable. This lack of portability

has inhibited a wide-spread use of MEG systems. The system 10 is portable and is

capable of operating in many or most clinical settings, in almost any room in a clinic

without electromagnetic shielding. In unshielded environments, there may be three

types of noise: (1) low frequency magnetic field changes due to the variation in the

earth's magnetic field, due to movements of cars, trains, etc., (2) line frequency noise

and (3) RF noise. Considering noise problems plus an additional problem of sampling

requirement, a new SQUID control unit manufactured by the Systemtechnik Ludwig

(STL), GmbH, Konstanz, Germany is currently preferred. The initial stage of noise

cancellation is accomplished by using first-order gradiometers which can reject uniform

magnetic fields with a rejection ratio of at least about 100:1. The second stage may be

accomplished by software cancellation, after recording the data. Fig. 19 illustrates the

cancellation of the ambient earth magnetic field changes that have been achieved in the frequency range below about 5 Hz. The data in square symbols ("before subtraction") illustrate the noise level sensed by a second-order gradiometer of liver iron

biosusceptometer installed in Torino, Italy. The reference channel in this case was a fluxgate magnetometer. The curve in triangles ("after subtraction") shows the same

curve with the same scale after the cancellation. The curve in diamonds ("after subtraction, x32") shows the noise-cancelled curve after magnifying it by a factor of 32

which corresponds to the ratio of the standard deviations of the signals before and after

the noise cancellation. The cancellation by a factor of about 30 achieved in our

preliminary work is comparable to the shielding factor of the commercially available two- layer magnetically shielded rooms in the frequency range below 1 Hz.

Figure 20 shows the noise cancellation for the line frequency noise using the 8

reference channels. Noise cancellation was performed on data from a 29 channel

gradiometer sensor array installed at the Vanderbilt University with an additional eight

channels of reference. The eight channels of reference consisted of five gradiometer channels and three magnetometer channels comprising a complete field and field gradient measurement. The test noise data was acquired at a 2 kHz sample rate for one

minute with no signal present. The noise was dominated by 60Hz line noise and its harmonics. A multivariate, linear, least-squares fit was applied to the first 30 sec of the

data to determine a linear functional dependence of the signal array channels on the

reference channels. The 29 by 8 matrix of fit coefficients was then applied to each time step in the second thirty seconds of the test data. This generated a prediction of the

noise in the sensor array channels that was then subtracted from the actual noise

measured. Over the 29 channels, it appears that a noise cancellation may be achieved under certain circumstances of up to 90. This noise cancellation scheme may be refined by finding the weights that may be time dependent. This refinement may provide a line

frequency cancellation by a factor of greater than about 100.

The data acquisition may be carried out by a PCI-based system that may be attached to the cart 14 as shown in Fig. 1. The outputs from the 84 SQUID control

units may be fed to a set of data routers via fiber optic cables. This reduces the rf noise feeding back into the SQUID control unit and into the SQUIDs. The control units are

housed in units of three. The fiber optic outputs from four units (12 channels) may be

fed at a rate of 480 kByte/sec to a level 1 router. Four of the level 1 routers are fed to the next router at a rate of 1.92 MB/sec. Since there are 84 channels, 7 level 1 routers

may be required for some applications feeding to two level 2 routers. The two outputs of

the level 2 routers may be fed into a PCI card with a transfer rate of 8 MB/s. This data

acquisition system continuously acquires 4-byte data at 10 kHz from 84 channels. A 1 GHz PCI-based PC may be is sufficient for some applications. The STL system may

work with the Windows NT. In some applications, such as in the studies aimed at measuring the 600 Hz

activity from the cortex, it is necessary to use a signal bandwidth of 3 kHz for some applications. Thus, the data may be sampled at a rate of at least 8 kHz. The data acquisition may be controlled by software. . It provides a complete control over all electronic features. An optical technique may be used to determine the head shape of

the infant. This method uses one digital camera to take the pictures of a grid pattern

projected onto the baby's head. The distortions of the grid pattern seen by the camera are used to reconstruct the 3D shape of the head and face. This method may be selected since it is completely remote in operation, non-invasive, fast and economical. The image can be obtained in less than 1 second and the reconstruction can be done offline, so that there is no need to worry about movement of the baby's head.

The conventional optical positioning system 28 from Eyetronics may be

employed. The accuracy better than 1 mm can be achieved. A conventional lithographic

technique is used to prepare the grid pattern. Only a single picture, taken from a slightly

different angle than the projection angle, may be sufficient to extract 3D shape

information. The input parameters are the relative positions of the camera and the miniature slide projector that may project a single grid pattern onto the face and head,

and the deformed grid on the object. To obtain a full 3D model of the head, several

overlapping pictures may be taken from different angles. A software, provided by Eyetronics, may be used to integrate the separate images. This process can be

completed before the EEG/MEG measurements start.

It may be important for some applications to be able to continuously monitor the position and orientation of the baby's head in order to maximize or at least increase the

time available for useful measurements. In studies involving normal, healthy babies, the presently preferred procedure involves no sedative. This means that the study may be

done while the baby is asleep. The duration of sleep is typically between about 10 min and about 40 min. Monitoring the head position continuously during this period enables

the data to be analyzed during the motion-free periods. The useful measurement period may also be extended due to the monitoring , to the period of wakefulness. Oftentimes

the baby keeps his/her head stationary for more than about 10 sec at a time during the

transition to the sleep state. Thus, it would be possible to measure the brain activity

during the awake stage if the baby's head can be continuously monitored. There are also other techniques available for both 3D head shape mapping and

head position tracking. For the head position tracking there are optical, electromagnetic and laser tracking systems. It may be desirable for some applications to continuously monitor the head with an absolute positional accuracy of about 1 mm during measurements.

Optical tracking

Optical tracking systems include two or more cameras of known locations. They track

three or more marks in 3D. The marks can be either passive (for example, reflective

tape) or active (for example, infrared LED's). Optical systems have 0.3 - 0.4 mm accuracy in a tracking volume of about 1 m³. The update rate is in the 20 - 70 Hz range.

Optical tracking does not tend to interfere with MEG measurements, so that the object

location can be synchronized with magnetic measurements.

Laser tracking Laser tracking system has the same advantage as optical systems in that it does not tend to interfere with magnetic measurements, and the object position can be synchronized with the MEG data. These systems include a cost effective LaserBird

system from Ascension Technology. The accuracy is about 1 mm at about 1 m distance.

The tracking is done by scanning the work area with a laser beam. The sensors attached

to a baby's head pick up the laser beam. From these data signals the information on the

object position is derived.

Electromagnetic tracking

Electromagnetic tracking systems are widely used with SQUID biomagnetic measurements (for example, EM tracking systems from Polhemus). An electromagnetic transmitter is rigidly attached relative to the pick up coils, and three receivers are

attached to the head. The accuracy of this system is on the order of about 1 mm.

CLUSTER SENSOR SHIELDED MEG SYSTEM

Referring now to Figs. 21 through 29, there is shown a high-resolution

magnetoencephalography (MEG) system 55 for evaluating neurological impairments of

preterm and term babies, for example. The system 55 is generally similar to the system

10, except that the system 55 employs clustered sensors instead of modular sensors,

and has other features such as being shielded in a particular manner.

The system 55 is adapted to serve as a non-invasive neurodiagnostic tool in

assessing possible neurological dysfunctions and brain development in neonates such

as a patient 57. System 55 includes a cart 59 having a headrest assembly 62 disposed

in an upwardly facing direction for receiving the head of the patient 57. The headrest

assembly 62 is generally similar to the headrest assembly 16, and includes a sensor

array generally indicated at 64 mounted below a concave headrest 66 similar to the

headrest 21, and as shown in Fig. 55. The cart 59 is designed to be portable and roll

along the ground on a set of wheels such as the wheels 68, 71 and 73.

A SQUID dewar 75 is mounted on the cart 57, and includes an optical positioning

system 76, which is similar to the optical positioning system 28 of Fig. 1 , for the purpose

of determining the position of the head of the patient 57. A bed or cushion 77 on the

upper surface of the cart 57 permits the patient 57 to lie in a reclined position with his or

her head supported from below by the headrest 62.

As best seen in Fig. 22, a liquid helium reservoir 79 of the SQUID dewar 75 is a

fill port 82 extending above the upper surface of the cart 57. SQUID data acquisition

electronic equipment 84 and SQUID phase lock loop electronic equipment 86 are mounted on the cart 57, together with a power hub 88. These electronic components

are mounted within a shielded container 91 to protect them against radio frequency

interference. The electronic components are connected to the SQUID via a group of

cables generally indicated at 92.

A portable trailer 93 is mounted rollably above the ground by means of a series of

wheels such as the wheel 94. A group of shielded cables generally indicated at 95

provide power and data channels for the electronic equipment mounted on the cart 57.

In this manner, when the cart 57 is moved to the desired location, the trailer including a

DC power supply 97 and a transformer 99 can be moved along with the cart 57. A pair

of personal computers 102 and 104 are mounted [on] the trailer 93 and communicate

with a notebook computer 106 mounted on top of the trailer 93 to be utilized by an

attendant.

The headrest assembly 62 has two curvatures for coronal and sagittal (axial)

coverage. As indicated in Figs. 24 and 25, the headrest assembly 62 is concave and is

configured in an ellipsoid shape having a sagittal radius of curvature of between about

80 mm and about 120 mm for the sagittal axis of the head and having a coronal radius

of curvature of between about 60 mm and about 90 mm at the coronal axis of the head.

A more preferred range of the sagittal radius is between about 90 mm and about 110

mm, and a more preferred range of the coronal radius is between about 70 mm and

about 80 mm. Currently, the most preferred sagittal radius is about 100 mm, and

currently the most preferred coronal radius is about 75 mm.

The headrest 66 is composed of non-metallic head-insulating structurally strong

material. This material is currently preferred to be fiberglass G 10. Each one of the sensors 64 is a superconducting gradiometer having a pick-up coil diameter of between about 4 mm and about 8 mm. More preferably, the pick-up coil diameter is between about 5 mm and about 7 mm. Currently, the most preferred pick-up diameter is about 6 mm.

The gradiometer sensors are uniformly distributed relatively to the head engageable surface of the headrest 66. Each one of the sensor pick-up coils being

spaced apart by a spacing distance of between about 6 mm and about 14 mm. This

spacing distance is more preferably between about 8 mm and about 12 mm. As

currently contemplated, the sensors are arranged in groups of four, wherein the spacing

distance between adjacent sensors of a group is about 8.5 mm and the spacing distance between diagonally disposed sensors of a group is about 12 mm.

Referring now to Figs. 26, 27 and 28, the sensors 64 are arranged in groups, and

the headrest 66 has a corresponding series of windows or recesses such as a recess 108 in the rear surface of the headrest 66 positioned opposite to one of the groups of the

sensors. In this regard, each one of the recesses is generally rectangular in shape and

is dimensioned to the approximate size of its group of sensors. In this regard, the rear surface of the headrest is arranged in a honeycomb configuration to provide a thin wall

construction for the sensors so that the sensors may be positioned in a close relationship to the head of the patient 57. The honeycomb configuration of the rear wall

of the headrest 66 is best seen in Fig. 28.

While the sensors 64 are arranged in clusters of four, it is to be understood that

there could be other numbers of such sensors clustered together. Also, it is contemplated that each separate sensor may have its own recess or window and not be

clustered with other sensors. In the currently preferred example, the sensors are arranged in groups of four, and each one of the four sensors of a group provides a

separate communication channel. The channel is usable individually, or in combination

or subtracted from one another. Thus, the channels can be summed in various

combinations for signal averaging purposes, albeit with a decrease in spatial resolution.

Additionally, the differences between channels can be taken, such as by electronic

subtraction of their respective voltages to effectively measure planar gradients.

Furthermore, the channels can be subtracted, or used individually.

The dewar 75 is radio frequency interference shielded by multiple techniques.

The external portions (those at room temperature) of the dewar is shielded by the

application of a thin coating or coatings of conductive material. The product of the

coating conductivity and thicknesses is such to provide an eddy current shield with a roll-

off frequency of less than 500 kHz. The coating may be applied through various

methods including (but not limited to), flame spraying or the use of a metallic enclosure,

as well as others. The interior portion of the dewar 75 is also shielded by the use of one

or more ultra-thin assemblies of conductive material, such as aluminum. The thickness

or thicknesses of the assemblies are such that they act as an eddy current shield with a

typical roll-off frequency of less than 500 kHz, but do not significantly attenuate magnetic

signals of interest (typically less than 10 kHz).

Additionally, the power cables DC power supply carts or trailer are filtered to

prevent radio frequency interference from entering either the electronics or the

magnetometer detection sensor coils in the dewar.

Headrest Constant Sensor Gap

Referring now to Fig. 29, the relative close spacing of the sensors 64 and the

headrest 66, is maintained constant through various temperature changes of the dewar 75. In this regard, when the system 10 either cools down or warms up, the differences in

the coefficient of thermal expansion of the various components may cause the small gap

between the sensors 64 and the headrest 66 to change in an undesirable manner.

Therefore, according to the disclosed embodiment of the present invention, the gap

between the sensors and the headrest remains substantially constant as a result of the

mounting structure for the headrest assembly 62.

A mounting ring 109 is fixed to the headrest assembly 62 and mounts it fixedly to

the dewar 75 in a rigid manner. A coil array plate 110 supports the sensors 64 in close

proximity to the headrest 66 as hereinbefore described. A set of rods such as the rods

111 , 112 and 113 support the plate 110 from below and have their lower ends

connected to an intermediate mounting ring 115. A set of shorter rods such as the rods

117, 118, 119 support the intermediate mounting ring 115 from above and are

connected to a fixed mounting ring 122. In this regard, the mounting ring 122 is fixed

with respect to the dewar 75. The longer rods such as the rod 111 is composed of

suitable material such as quartz so that when the system 10 cools down, the quartz rods

shrink in length to pull the coil array plate 110 away from the headrest 66 to thereby

increase lift-off. However, the shorter rods such as the rod 117 are also composed of

suitable material such as quartz so that when the system cools down, for example, the

quartz rods such as the rod 117 shrinks in length to pull the coil toward the headrest 66.

In this regard, the longer and shorter rods compensate one another for temperature

changes to help maintain a constant gap between the sensors and the headrest.

The rods are composed of quartz material since quartz has a low characteristic of

thermal contraction between room temperature and cryogenic temperatures. Additionally, the coil array plate 110 is pre-adjusted to correct lift-off when the system is warm.

While particular embodiments of the present invention have been disclosed, it is

to be understood that various different modifications and combinations are possible and

are contemplated within the true spirit and scope of the invention. There is no intention,

therefore, of limitations to the exact disclosure herein presented.

Claims

WHAT IS CLAIMED IS:

1. A magnetoencephalography system, comprising:

a portable cart for moving along the ground;

a SQUID dewar mounted in an inverted manner on the cart;

a headrest assembly mounted on the cart and having a headrest for

supporting a head of a patient and forming a portion of the dewar;

the headrest assembly includes an array of magnetic sensors of the

SQUID dewar for responding to electrical activity of the brain of the head; and

a patient bed mounted on the cart adjacent to the headrest for supporting

the body of the patient with his or her head supported by the headrest.

2. A magnetoencephalography system according to claim 1 , wherein said

headrest is concave and is configured in an ellipsoid shape having a sagittal radius of

curvature of between about 80 millimeters and about 120 millimeters for the sagittal axis

of the head and having a coronal radius of curvature of between about 60 millimeters

and about 90 millimeters at the coronal axis of the head.

3. A magnetoencephalography system according to claim 2, wherein the

sagittal radius is between about 90 millimeters and about 110 millimeters, and wherein

the coronal radius is between about 70 millimeters and about 80 millimeters.

4. A magnetoencephalography system according to claim 3, wherein said

sagittal radius is about 100 millimeters, and wherein the coronal radius is about 75

millimeters.

5. A magnetoencephalography system according to claim 1 , wherein the

headrest is composed of non-metallic head-insulating structurally strong material.

6. A magnetoencephalography system according to claim 5, wherein said material is G-10 fiberglass.

7. A magnetoencephalography system according to claim 1 , wherein each

one of said sensors is disposed at a spacing distance from the outer head engaging surface of between about one millimeter and about three millimeters.

8. A magnetoencephalography system according to claim 7, wherein said

spacing distance is between about one millimeter and about two millimeters.

9. A magnetoencephalography system according to claim 1 , wherein each

one of said sensors is disposed at a spacing distance of greater than about one

millimeter from the outer head engaging surface of the headrest assembly.

10. A magnetoencephalography system according to claim 1 , wherein each

one of said sensors is a superconducting gradiometer having a pick-up coil diameter of

between about four millimeters and about eight millimeters.

11. A magnetoencephalography system according to claim 10, wherein said

pick-up coil diameter of between about five millimeters and about seven millimeters.

12. A magnetoencephalography system according to claim 11 , wherein said

pick-up diameter is about six millimeters.

13. A magnetoencephalography system according to claim 1 , wherein each

one of said sensors is a superconducting gradiometer having a pick-up coil, said sensors being substantially uniformly distributed relative to the head engageable surface of the

headrest, each one of the sensor pick-up coils being spaced apart by a spacing distance

of between about 6 millimeters and about 14 millimeters.

14. A magnetoencephalography system according to claim 13, wherein said spacing distance is between about 8 millimeters and about 12 millimeters.

15. A magnetoencephalography system according to claim 13, wherein said

sensors are arranged in groups of four, wherein the spacing distance between adjacent

sensors of a group is about 8.5 millimeters and the spacing distance between diagonally

disposed sensors of a group is about 12 millimeters.

16. A magnetoencephalography system according to claim 1 , wherein said

sensors are arranged in groups thereof, and wherein said headrest has a corresponding

series of recesses in the rear surface thereof positioned opposite to said groups of said

sensors.

17. A magnetoencephalography system according to claim 16, wherein each

one of said recesses is dimensioned to the approximate size of its group of sensors.

18. A magnetoencephalography system according to claim 17, wherein said

recesses are arranged in a honeycomb configuration.

19. A magnetoencephalography system according to claim 18, wherein each

one of said group comprises four sensors.

20. A magnetoencephalography system according to claim 1 , wherein said

sensors are arranged in groups of four, each one of said four sensors of a group

provides a separate communication channel, the channels being useable individually, or

combined or subtracted.

21. A magnetoencephalography system according to claim 1 , wherein said cart

includes electronic equipment for data acquisition from said sensors, and further

including a container composed of conductive material for confining said electronic

equipment to shield it from radio frequency interference.

22. A magnetoencephalography system according to claim 21 , wherein said

dewar has an external coating of conductive material for radio frequency interference

shielding.

23. A magnetoencephalography system according to claim 21 , further

including a direct current power supply for supplying electrical power to said electronic

equipment.

24. A magnetoencephalography system according to claim 23, further

including a trailer having said power supply mounted thereon and being connected

mechanically to said cart.

25. A headrest assembly for a magnetoencephalography system, comprising:

a concave headrest assembly having a headrest for supporting a head of a

patient;

an array of ultra high spatial resolution cryocooled superconducting

sensors disposed adjacent to the headrest for responding to electrical activity of the

brain of the head; and

said headrest being configured in an elipsoid shape having a sagittal

radius of curvature of between about 80 millimeters and about 100 millimeters for the

sagittal axis of the head and having a coronal radius of curvature of between about 60

millimeters and about 90 millimeters at the coronal axis of the head.

26. A headrest assembly according to claim 25, wherein said headrest is

concave and is configured in an ellipsoid shape having a sagittal radius of curvature of

between about 80 millimeters and about 120 millimeters for the sagittal axis of the head

and having a coronal radius of curvature of between about 60 millimeters and about 90

millimeters at the coronal axis of the head.

27. A headrest assembly according to claim 26, wherein the sagittal radius is

between about 90 millimeters and about 110 millimeters, and wherein the coronal radius

is between about 70 millimeters and about 80 millimeters.

28. A headrest assembly according to claim 27, wherein said sagittal radius is

about 100 millimeters, and wherein the coronal radius is about 75 millimeters.

29. A headrest assembly according to claim 25, wherein the headrest is

composed of non-metallic head-insulating structurally strong material.

30. A headrest assembly according to claim 29, wherein said material is G-10

fiberglass.

31. A headrest assembly according to claim 25, wherein each one of said

sensors is disposed at a spacing distance from the outer head engaging surface of

between about one millimeter and about three millimeters.

32. A headrest assembly according to claim 31 , wherein said spacing distance

is between about one millimeter and about two millimeters.

33. A headrest assembly according to claim 25, wherein each one of said

sensors is disposed at a spacing distance of greater than about one millimeter.

34. A headrest assembly according to claim 25, wherein each one of said

sensors is a superconducting gradiometer having a pick-up coil diameter of between

about four millimeters and about eight millimeters.

35. A headrest assembly according to claim 34, wherein said pick-up coil

diameter of between about five millimeters and about seven millimeters.

36. A headrest assembly according to claim 35, wherein said pick-up diameter

is about six millimeters.

37. A method of magnatoencephalography for the brain of a head of a patient,

comprising: supporting the head on a headrest assembly including a headrest mounted

on a cart having an array of magnetic sensors forming a part of an inverted SQUID

dewar; supporting the body of the patient on a bed mounted on the cart; and detecting

electrical activity of the brain of the patient.

38. A method according to claim 37, further including moving the headrest and

the sensors relative to one another to positionally adjusting them.

39. A mounting arrangement for a magnetoencephalography system headrest

assembly forming a portion of a SQUID dewar and having a fixed headrest and an array

of sensors, comprising:

a sensor array plate for positioning the sensors relative to the headrest;

an intermediate moveable mounting member;

a plurality of first rods interconnecting said array plate and said moveable

mounting member, each one of said rods being composed of material expandable and

contractible with changes in temperature; and

a plurality of second rods fixed at one of their ends relative to the dewar

and being connected at their opposite ends to said moveable mounting member, said

second rods being composed of said material;

whereby said moveable mounting member tends to be moved in one

direction toward or away from said sensor array plate, and tends to be moved in an

opposite direction away from or toward said array plate resulting in temperature changes

affecting the first and second rods, so that said sensor array plate and its sensors

maintain a substantially constant spacing between said sensors and said headrest with

changes in temperature.

40. A mounting arrangement according to claim 39, wherein said first and

second rods are each composed of quartz material.

41. A mounting arrangement according to claim 39, wherein said sensor array plate is supported from below by said first and second rods.

42. A mounting arrangement according to claim 39, wherein said moveable

mounting member is positioned below said sensor array plate and said second rods

extend upwardly therefrom.

43. A mounting arrangement according to claim 42, wherein said moveable

mounting member is a ring.

44. A mounting arrangement according to claim 39, further including a fixed

mounting ring rigidly attached to the dewar.

45. A mounting arrangement according to claim 39, wherein said headrest

assembly being fixedly attached to the dewar.

46. A method of mounting a headrest and an array of sensors to a SQUID

dewar of a magnetoencephalography system, comprising:

positioning the sensors relative to the headrest with a sensor array plate; interconnecting the sensor array plate and an intermediate moveable

mounting member with a plurality of first rods, each one of said rods being composed of material expandable and contractible with changes in temperature; and interconnecting the moveable mounting member and the dewar with a

plurality of second rods, each one of said second rods being composed of said material;

whereby said moveable mounting member tends to be moved in one direction toward or away from the sensor array plate, and tends to be moved in an

opposite direction away from or toward said array plate resulting in temperature changes affecting the first and second rods, so that said sensor array plate and its sensors

maintain a substantially constant spacing between said sensors and said headrest with

changes in temperature.

47. A method according to claim 46, wherein said sensor array plate is

supported from below by said first and second rods.

48. A method according to claim46, wherein said moveable mounting member

is positioned below said sensor array plate and said second rods extend upwardly

therefrom.

49. A method according to claim 48, further including rigidly attaching the

headrest to the dewar.